The fetal origins of osteoporotic fracture

Undemutrition and other adverse influences arising in fetal life or immediately after birth have a permanent effect on body structure, physiology, and metabolism. The specific effects of undernutrition depend on the time and development at which it occurs; rapidly growing fetuses and neonates are more vulnerable. Its effects include altered gene expression, reduced cell numbers, imbalance between cell types, altered organ structure, and changes in the pattern of hormonal release and tissue sensitivity to these hormones. Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture. Body weight in infancy is a determinant of adult bone mineral content, as well as of the basal levels of activity of the GH/IGF-1 and HPA axes. Epidemiological studies have suggested that maternal smoking and nutrition during pregnancy influence intrauterine skeletal mineralization. Finally, childhood growth rates have been directly linked to the risk of hip fracture many decades later. Further studies of this phenomenon are required in order that effective preventive strategies against osteoporosis throughout the life course may be delineated and more effectively applied.